The moves come as the industry witnesses a downturn in some of its major Asian markets to go alongside difficulties in Europe, and amid speculation about the double-G brand's search for identity in the post-logo era.
Florence-based Gucci, which analysts say is responsible for two-thirds of Kering's profits, saw third-quarter revenues drop 2 per cent to 851 million euros ($1.05 billion). Shares in Kering closed down 2 per cent at 155.65 euros.
Giannini will step down as creative director, a post she has held since 2006, after showing her fall/winter 2014-2015 collections for men in January and women in February. No replacement was immediately announced. She joined Gucci in 2002 as the lead designer for leather goods, adding women's ready-to-wear in 2005, before being named the sole creative director.
Di Marco leaves his post at the end of the year after 13 years with the group, first as CEO of Bottega Veneta, another brand in the company's stable. He will be replaced by Marco Bizzarri.
Giannini and di Marco are also partners and the parents of a young daughter.
Kering Chairman and CEO Francois-Henri Pinault heaped praise on both and noted Giannini's "remarkable accomplishment" of having overseen all aspects of the global brand's image and products for nearly a decade. Kering credited di Marco with making Gucci among the best-performing brands in the luxury industry.
Pinault has been a fixture in the Gucci front-row during Milan Fashion Week, often with his wife, Selma Hayak Pinault, who is both a friend of Giannini's and a fan of her designs.
An earlier version of this story incorrectly spelled the name Patrizio di Marco.